A Modular In Vitro Platform for the Production of Terpenes and Polyketides from CO₂

A long-term goal in realizing a sustainable biocatalysis and organic synthesis is the direct use of the greenhouse gas CO₂ as feedstock for the production of bulk and fine chemicals, such as pharmaceuticals, fragrances and food additives. Here we developed a modular in vitro platform for the continuous conversion of CO₂ into complex multi-carbon compounds, such as monoterpenes (C₁₀ ), sesquiterpenes (C₁₅ ) and polyketides. Combining natural and synthetic metabolic pathway modules, we established a route from CO₂ into the key intermediates acetyl- and malonyl-CoA, which can be subsequently diversified through the action of different terpene and polyketide synthases. Our proof-of-principle study demonstrates the simultaneous operation of different metabolic modules comprising of up to 29 enzymes in one pot, which paves the way for developing and optimizing synthesis routes for the generation of complex CO₂ -based chemicals in the future.